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 Journal of Clinical Lipidology

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Lipid.Org Call for Submissions - Topic Listing

Lipoproteins, Atherosclerosis, and Risk Reduction - Basics

  1. Lipoprotein risk factors, including lipoprotein(a)
  2. Atherosclerosis, the cause of heart attack and stroke
    • High LDL conc'n in arterial intima
    • Development of foam cells
    • Development of atherosclerotic core
    • Plaque formation
    • Plaque rupture and the vulnerable plaque
  3. Warning signs of heart disease, arteriosclerosis, and stroke
    • Chest pain - also unexplained SOB, throat pain, etc.
    • Transient ischemic attacks
    • Claudication
    • Aortic aneurysms, dissection and rupture
    • Family history
    • Lack of warning signs
  4. ** National Cholesterol Education Program guidelines
    • Web sites
    • Guidelines to promote evidence-based standard of care
    • ATP and pediatric guidelines aimed at primary care physicians
    • Limitations of the guidelines - role of lipid clinics
    • Focus on LDL cholesterol
    • Screening total and HDL cholesterol
    • Risk factor assessment
    • Measurement of fasting lipoproteins
    • Treatment algorithms
    • Dietary treatment, refer to topic below
    • Drug treatment, usually beginning with a statin
  5. Risk reduction - an overview
    • Based on AHA Consensus Statement
    • Estimate the level of protection
    • Add a note on omega 3 fatty acids
  6. Reducing stroke risk by treating cholesterol and triglycerides
    • Surprising results with statins, conclusive evidence
    • Gemfibrozil, the VA-HIT study
    • Niacin, a look back at the Coronary Drug Project
    • Web sites, overall treatment of stroke and TIA

Dyslipidemia Types and Diagnoses

  1. Focus on low density lipoprotein (LDL) cholesterol, the "bad cholesterol"
    • Epidemiologic evidence, total and LDL cholesterol
    • Role of LDL in the arterial wall
    • Heterozygous and homozygous familial hypercholesterolemia
    • Major statin trials
    • Support for NCEP guidelines
    • Is lower better?
    • Is lowering LDL enough?
    • How low is too low? Evaluation of the evidence
    • Web sites
  2. High density lipoprotein (HDL) cholesterol, the "good cholesterol"
    • Epidemiologic evidence
    • Reverse cholesterol transport
    • Other beneficial effects of HDL
    • Complexity of HDL, apoA-I Milano and other paradoxes
    • Lifestyle and dietary measures to raise HDL
    • Role of oral estrogen, HERS and WHI studies
    • Early trials with niacin, CDP and Stockholm study
    • VA-HIT
    • Preliminary results from HATS
    • Conclusion - an unproven, but promising strategy
    • Web sites?
  3. High triglycerides and coronary heart risk
    • Austin's meta-analysis
    • University of Maryland study
    • Greater effects in women and in diabetic patients
    • Hypertriglyceridemia and small dense LDL
    • Mechanisms
    • Treatment of high triglycerides (refer below for dietary treatment)
  4. Familial hypercholesterolemia
    • An autosomal dominant disorder
    • LDL receptor defect - frequency, diagnosis, xanthomas, prognosis
    • Defective apolipoprotein B - less frequent, fewer criteria for clinical distinction, usual lack of xanthomas
    • Treatment - Step 2 or more intensive diet
    • Treatment - pediatric
    • Treatment - women of childbearing potential
    • Treatment - combination drug therapy (refer below)
    • MED-PED and Inherited High Cholesterol Foundation, phone no. and web site (?)
  5. Type III hyperlipidemia
    • Remnant lipoproteins
    • Relationship to apolipoprotein E
    • Necessity for another factor
    • Xanthomas - tendinous and tuberous
    • Atherogenicity
    • Treatment
  6. Triglyceride levels over 1,000 mg/dl
    • Childhood onset versus adult onset
    • Milky plasma
    • Pancreatitis
    • Other features of chylomicronemia syndrome
    • Relationship to diabetes, alcohol, lipodystrophy
    • When is hospitalization required?
    • Dietary management depending on triglyceride level
    • Drug treatment
    • Risk of atherosclerosis
    • Frequent measurement of triglycerides
  7. Small dense LDL, lipoprotein size and subfraction analysis
    • Size range of LDL
    • LDL particle concentration
    • Epidemiologic evidence
    • Theories about atherogenicity
    • Relationship to triglycerides
    • Triglycerides in VLDL cause triglyceride enrichment of LDL
    • Lipase action removes triglyceride from LDL, reducing particle size
    • Treatment of small dense LDL by reducing plasma triglycerides
    • Treatment of small dense LDL by lowering all LDL
    • When is it appropriate to measure lipoprotein subfractions?
    • Do we know that treatment works? No, but...
    • VLDL and HDL subfractions, much less is known
    • Laboratories and web sites
  8. Lipoprotein(a), a hidden risk factor for heart disease and stroke
    • What lipoprotein(a) is
    • Lipoprotein(a) in the atherosclerotic plaque
    • Relationship to plasminogen
    • Animal evidence for inhibition of fibrinolysis
    • Skewed distribution of lipoprotein(a) in most ethnic groups
    • Epidemiology - predictive power comparable to LDL and HDL
    • Epidemiology - lipoprotein(a) interaction with other risk factors
    • Is lipoprotein(a) a risk factor by itself?
    • Blacks, twice the levels as others, but not twice the risk
    • If only one normal range is given, double it for blacks
    • Difficulties with laboratory analysis
    • Reduction of lipoprotein(a) by niacin and oral estrogen
    • Usually one cannot achieve "normal" lipoprotein(a) levels
    • When is it appropriate to measure lipoprotein(a)?
    • When and how would a lipoprotein(a) level affect clinical decision-making?
    • Chief strategy - use lipoprotein(a) as a additional risk factor to govern LDLC goal

Dietary and Lifestyle Treatment

  1. ** NCEP guidelines for dietary treatment of dyslipidemia
    • NCEP website
    • Other helpful websites
    • One diet, two steps
    • Saturated fat and trans fatty acids
    • Monounsaturated fat
    • Polyunsaturated fat
    • Cholesterol
    • Increase fiber
    • Achieve ideal body weight
  2. Dietary treatment of high cholesterol
    • Follow outline of Grundy and Denke
  3. Dietary and lifestyle treatment of high triglycerides
    • Triglyceride, a storage and transport form for fatty acids
    • Triglyceride in body stores, fatty acids in blood, triglyceride in blood
    • Overweight and obesity
    • Role of alcohol - alcohol might not prevent CHD in patients with high triglycerides
    • Exercise
    • Dietary carbohydrate
    • Glycemic index
    • Relationship to diabetes - refer to prevention of Type 2 Diabetes
  4. Alternative and intensive nutritional treatment to prevent heart disease and stroke
    • Epidemiologic data - undeveloped peoples
    • Epidemiologic data - Japanese migration
    • Epidemiologic data - lipids in U.S. vegetarians
    • Lifestyle Heart Trial
    • Follow-up of Lifestyle Heart Trial
    • Lifestyle Prevention Study (Ornish Dec. 1998)
    • Conclusions on vegans diet
    • Seven Countries study
    • Lyon Diet Heart study
    • Alternative intensive nutritional treatment - Mediterranean Diet
    • Michael Oliver - unsaturated fats
    • Overall summary - some of the best results in atherosclerosis prevention and treatment have come in dietary trials
  5. ** Weight reduction - some basic principles
    • Assume the reader wants to lose weight
    • Quick review of reasons for losing weight
    • Effects on lipoproteins
    • Fat is stored energy
    • Size of the fuel tank - how long can a person live without any calories?
    • Disconnection between availability of chemical energy and the feeling of vigor and energy
    • Size of intra-abdominal deposits
    • Even 5 to 10 pounds of weight reduction can have a significant impact on metabolic parameters
    • Role of exercise - number of calories burned
    • Role of exercise - restoring the feeling of vigor
    • Hitting the wall, downregulation of basal metabolic rate
    • Maintaining weight reduction, frequency of weighing
    • Accentuating positives
    • Writing everything down
  6. Weight reduction - annotated guide to web sites
  7. Weight reduction - alternative strategies
  8. Exercise for people with heart disease or high risk
    • Classic studies
    • Outcomes from studies at the Cooper Clinic
    • Effect of walking, Nurses Health Study (NEJM)
    • Mechanisms of improvements in cardiovascular risk
    • Increased HDL
    • Aerobic exercise, increased coronary blood flow, and coronary dilation
    • Standard recommendations - minimum 30 minutes 3 times a week
    • Estimates of calories expended
    • Recognizing risks of cardiac arrhythmia
    • When to have a stress test performed
    • Importance of warm-up and cool-down times
    • Musculoskeletal injuries - web sites
    • Equipment - web sites
    • Go ahead and do it!
  9. Omega 3 fatty acids and prevention of sudden death
    • It is almost proven that small doses of omega 3 fatty acids can prevent 20-30% of deaths in people with heart disease. Omega 3 fatty acids can be obtained by eating fatty fish or certain plant oils, or by taking 1-3 capsules per day with essentially no side effects.
    • Epidemiology of fish intake and heart disease
    • What is an omega 3 fatty acid?
    • Diet and Reinfarction Trial
    • Seattle study and Physicians Health Study, 50% reduction of sudden death
    • Sudden death is caused by ventricular fibrillation in almost all cases
    • Animal studies on prevention of ventricular fibrillation by omega 3 fatty acids
    • GISSI Prevention Study
    • Possibility that alpha linolenic acid may also be protective
    • Lyon Diet Heart Study
    • Is it proven? No. Lack of placebo group in GISSI
    • Do we wait for proof? Yes, we'll wait before establishing national guidelines. However, the purpose of this communication is to show and explain the available data, and let each person make up his or her mind.
    • Sources of fish oil - recommend one to three capsules daily
    • Not cod liver oil
    • Take fish oil before meals to reduce fishy smell with belching
    • Sources of alpha linolenic acid - canola, soybean, flaxseed oils, especially flaxseed oil
    • Other effects of fish oil - only long chain omega 3 fatty acids lower triglyceride levels
    • Other effects of fish oil - only EPA has anti-inflammatory properties
    • Other effects of fish oil - cancer prevention in animal studies

Drug Treatment

  1. Overview of drug therapy for prevention and treatment of atherosclerosis
    • Key questions - does it work? Double-blind, placebo-controlled randomized trials. Explain each of the terms.
    • Ranking the drugs in terms of level of proof
    • Key questions - what are the risks of side effects?
    • No clear case of permanent liver damage from statin monotherapy
    • Key questions - how much does it cost?
    • Cost of coronary heart disease and stroke
    • Cost of medications
    • Reducing overall costs or delaying costs?
    • Cost per year of life saved
    • Statin treatment
    • Niacin, the least expensive treatment
    • Gemfibrozil for low HDL
    • High triglyceride - no clear studies yet
    • Cost per year of treatment
  2. ** Statin treatment of high cholesterol
    • Statins are the best proven and best tolerated anti-atherosclerotic drugs
    • Web sites
    • a.k.a. HMG CoA reductase inhibitors
    • Major effect on LDLC, also beneficial effects on HDLC and triglycerides
    • Names of statin drugs
    • 5 major studies
    • A major unanswered question for clinical research - how low should the LDLC goal be?
    • HMG CoA reductase and mevalonic acid
    • Monitoring of liver function, rarity of liver damage
    • Rare instances of skeletal muscle damage and breakdown
    • Infrequent instances of myalgias, more commonly due to something else
    • Rare side effects listed in drug labeling - web sites
    • Possibility of long-term harmful effects (very unlikely to exceed long-term benefit for heart disease and stroke)
    • Possibility of unanticipated long-term benefit of increasing bone density
    • Differences among statins - strength of effect
    • Differences among statins - strength of evidence (The prescribing provider may consider...)
    • Differences among statins - minimal evidence for differences in tolerability, switch classes or move to a lower strength if myalgias is a problem (The prescribing provider may consider...)
    • How to take statins
    • Drug interactions
  3. ** Niacin, improvement of all lipoprotein parameters
    • Niacin is the best drug for raising HDLC, is the first to have been shown clearly to prevent heart attacks, and is the least expensive drug for prevention and treatment of atherosclerosis
    • Side effects, most commonly flushing, have sharply limited the use of niacin in clinical practice. However, flushing can usually be avoided. Recent progress has been made in this area.
    • Niacin and niacinamide (synonyms nicotinic acid and nicotinamide) are vitamin B3. At high doses only niacin affects lipoprotein levels; niacinamide does not. Doses of niacin used to treat dyslipidemia are 20-200 times the vitamin dose. At these high doses, niacin has some rare, but serious, side effects. You should never think that you are "just taking a vitamin" when you take niacin in high doses. It is a drug and should always be taken under supervision of a physician (or another health care provider who works directly under a physician). The Food and Drug Administration should regulate the use of niacin at doses over 100 mg, but thus far has chosen not to do so.
  4. ** Bile acid binders for reducing cholesterol
  5. ** Gemfibrozil and fenofibrate
  6. ** Combination drug therapy for dyslipidemia

Other Risk Factors - Diabetes Mellitus, Homocysteine, and C-Reactive Protein

  1. ** Risk of developing Type 2 Diabetes, and how to prevent it
    • Type 2 Diabetes Mellitus, diagnostic criteria, distinction from Type 1, prevalence, and importance (more info at ADA and other web sites)
    • Complications of Type 2 Diabetes
    • Risk based on family history
    • Risk based on triglyceride level, overweight, diabetes in pregnancy
    • Four lifestyle measures
    • Exercise
    • Weight control
    • Foods of low glycemic index (web sites)
    • Dietary fiber
    • Potential for medication to prevent Type 2 Diabetes
  2. ** Lipid treatment in diabetes
    • Definition of Type 2 Diabetes, risk of coronary events
    • Definition of Type 1 Diabetes, risk of coronary events
    • Diabetic dyslipidemia
    • ADA recommendations
    • Statins for LDLC treatment in diabetes
    • Gemfibrozil and fenofibrate in diabetes
    • Niacin in diabetes
    • Combination drug treatment of dyslipidemia in diabetes
  3. Homocysteine, a new atherosclerotic risk factor
    • Homocysteine, an amino acid, related to risk of heart disease and stroke
    • HC is not a lipoprotein, is not one of the 20 amino acids that are building blocks for protein, but is in the breakdown pathway for methionine.
    • Methionine, homocysteine, and 3 key vitamins are involved in a complicated series of chemical reactions that transfer a methyl group (a single carbon unit) between biological molecules. The 3 vitamins are...
    • How might HC increase atherosclerosis? Not known, but ...By damaging endothelium, the thin layer of cells that forms the inner lining of blood vessels. By promoting oxidation reactions.
    • Giving extra folic acid lowers HC...also called folate
    • You cannot get 400 micrograms of folic acid in the diet
    • Every daily multivitamin pill contains 400 micrograms... (Federal regulations state that the highest amount ...
    • There are no harmful side effects of taking vitamin mixtures at doses ordinarily found in a daily multivitamin pill.
    • Therefore, SELA providers commonly suggest that patients take a multivitamin every day.
    • Will a multivitamin every day really prevent heart attacks and strokes? Seven ongoing trials
    • Until results are available from these trials, most SELA providers feel that homocysteine measurements are not needed in the typical patient with heart disease or stroke.
    • What about taking higher doses of folic acid or adding high doses of vitamin B6 (pyridoxine) and vitamin B12?
    • Anything on dose responsiveness to higher doses of folic acid???
    • First, there is a rare disorder, called homcystinuria... Patients with homocystinuria sometimes benefit from B6. Because of its success in some of the rare patients with homocystinuria, B6 is sometimes used to treat the more common condition of high homocysteine levels in blood.
    • However, B6 might cause numbness or tingling in hands or feet, or even permanent nerve damage, especially when the dose is higher than 50 mg daily.
    • Second, blood homocysteine levels can be extremely high in a disease called pernicious anemia, which results from a lack of vitamin B12 in the body. In true cases of pernicious anemia, the body cannot absorb vitamin B12, no matter how much is taken in food or in pills. Therefore, pernicious anemia is treated with monthly injections of vitamin B12. When it is treated, blood homocysteine levels go down. Because of the relationship between vitamin B12 and homocysteine in pernicious anemia, vitamin B12 in doses of 100 to 200 mcg, taken by mouth, are sometimes recommended when a person simply has high homocysteine levels in the blood.
    • Explain the risk of masking pernicious anemia...
  4. C-reactive protein (CRP) and the role of inflammation in atherosclerosis
    • New risk factor
    • What is the relationship?
    • CRP an acute phase reactant
    • First possibility - CRP is directly involved in atherosclerosis
    • Second possibility - CRP shows that inflammatory responses in the body have a heightened state of activity. Inflammation promotes atherosclerosis.
    • Third possibility - one or more infectious agents raise CRP levels and also promote atherosclerosis, latest results show no impact of using antibiotics
    • Fourth possibility - since atherosclerosis itself has inflammatory cells producing inflammatory cytokines (define this), the high levels of CRP may simply be a result of atherosclerosis.
    • Should our treatment strategies try to reduce CRP levels? No, treatment strategies should be aimed at what we know to be useful and what we know about atherosclerosis development. However, CRP has opened up an interesting area of clinical research, which should be pursued further.

Other Key Drugs for Treating Atherosclerotic Disease

  1. ** Key role of aspirin in preventing heart attack and stroke
  2. Beta blockers, value in heart disease
  3. Angiotensin converting enzyme (ACE) inhibitors, value in heart disease

Research and Future Prospects

  1. What the future may hold
  2. Participation in research studies

Lipid Clinics

  1. Southeast Lipid Association and other lipid clinic groups
  2. Who might need to go to a lipid clinic?

Tell Us What You Think

Glossary of Medical Terms

  • Dyslipidemia, atherosclerosis, myocardial infarction, ischemia